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Rapid evolution of major histocompatibility complex Class I genes in primates generates new disease alleles in humans via hitchhiking diversity
Journal article   Peer reviewed

Rapid evolution of major histocompatibility complex Class I genes in primates generates new disease alleles in humans via hitchhiking diversity

T. Shiina, M. Ota, S. Shimizu, Y. Katsuyama, N. Hashimoto, M. Takasu, T. Anzai, J. Kulski, E. Kikkawa, T. Naruse, …
Genetics, Vol.173(3), pp.1555-1570
2006
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Abstract

A plausible explanation for many MHC-linked diseases is lacking. Sequencing of the MHC class I region (coding units or full contigs) in several human and nonhuman primate haplotypes allowed an analysis of single nucleotide variations (SNV) across this entire segment. This diversity was not evenly distributed. It was rather concentrated within two gene-rich clusters. These were each centered, but importantly not limited to, the antigen-presenting HLA-A and HLA-B/-C loci. Rapid evolution of MHC-I alleles, as evidenced by an unusually high number of haplotype-specific (hs) and hypervariable (hv) (which could not be traced to a single species or haplotype) SNVs within the classical MHC-I, seems to have not only hitchhiked alleles within nearby genes, but also hitchhiked deleterious mutations in these same unrelated loci. The overrepresentation of a fraction of these hvSNV (hv1SNV) along with hsSNV, as compared to those that appear to have been maintained throughout primate evolution (trans-species diversity; tsSNV; included within hv2SNV) tends to establish that the majority of the MHC polymorphism is de novo (species specific). This is most likely reminiscent of the fact that these hsSNV and hv1SNV have been selected in adaptation to the constantly evolving microbial antigenic repertoire.

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Collaboration types
Industry collaboration
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.6 Immunology
1.6.607 MHC Diversity
Web Of Science research areas
Genetics & Heredity
ESI research areas
Molecular Biology & Genetics
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